The studies proposed in this application are designed to answer a variety of questions relating to the neural control of the cardiovascular system in the disease state of congestive heart failure. We will determine if abnormalities in carotid sinus baroreceptor discharge exist in dogs with two models of low output heart failure (pulmonary artery stenosis plus tricuspid avulsion and chronic tachycardia) compared to sham operated animals. Single units from carotid sinus nerve will be recorded in these experiments. In addition, measurement of carotid sinus volume and diameter will be done in order to assess changes in compliance. In companion studies, the isolated carotid sinus technique will be used to look at the carotid sinus reflex control of the peripheral vasculature in as quantitative a manner as is possible in conscious dogs with and without heart failure. The baroreflex control of renal sympathetic nerve activity will also be investigated in conscious dogs with heart failure. The isolated carotid sinus technique will allow local perfusion of the carotid sinuses so that the effects of agents such as cardiac glycosides can be studied without complicating the experiments with their systemic effects. In subsequent studies, the role of cardiac receptor stimulation on the baroreflex control of regional resistances and sympathetic nerve activity will be studied to determine if input from these receptors (atrial and ventricular) alter the baroreflex in heart failure. In addition, the effects of selective cardiac receptor stimulation on sympathetic nerve activity will be assessed in dogs with chronic heart failure. Finally, in order to test the hypothesis that the salt and water retention of heart failure is mediated, in part, by exaggerated tubular responses to renal nerve activity, dogs with and without heart failure will be subjected to low level renal nerve stimulation or to reflex activation of renal sympathetic nerves while measuring salt and water excretion as well as GFR and renal blood flow. These studies will be carried out in the basal state and during plasma volume expansion in order to augment sodium excretion. In addition, the effects of bilateral renal denervation on renal function will be investigated in dogs with heart failure. This 5-year program represents a multidisciplinary approach to investigate the reflex abnormalities which may contribute to the symptomatology of chronic heart failure.